Abstract
The differentiation of naive CD4 T cells into specific effector subsets is controlled in large part by the milieu of cytokines present during their initial encounter with Ag. Cytokines that drive differentiation of the newly described Th17 lineage have been characterized in vitro, but the cytokines that prime commitment to this lineage in response to infection in vivo are less clear. Listeria monocytogenes (Lm) induces a strong Th1 response in wild-type mice. By contrast, we demonstrate that in the absence of IL-12p40 (or IFN-gamma) and type I IFN receptor signaling, the Th1 Ag-specific CD4 T cell response is virtually abolished and replaced by a relatively low magnitude Th17-dominated response. This Th17 response was dependent on TGF-beta and IL-6. Despite this change in CD4 T cell response, neither the kinetics of the CD4 and CD8 T cell responses, the quality of the CD8 T cell response, nor the ability of CD8 T cells to mediate protection were affected. Thus, generation of protective CD8 T cell immunity was resilient to perturbations that replace a strong Th1-dominated to a reduced magnitude Th17-dominated Ag-specific CD4 T cell response.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / microbiology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / pathology
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cells, Cultured
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Growth Inhibitors / physiology
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Immunity, Cellular / genetics
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Interferon Type I / physiology
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Interferon-gamma / physiology
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Interleukin-12 Subunit p40 / deficiency*
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Interleukin-12 Subunit p40 / genetics
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Interleukin-12 Subunit p40 / physiology
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Interleukin-17 / antagonists & inhibitors
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Interleukin-17 / physiology*
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Listeriosis / immunology
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Listeriosis / metabolism
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Listeriosis / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptor, Interferon alpha-beta / deficiency*
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Receptor, Interferon alpha-beta / genetics
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Receptor, Interferon alpha-beta / physiology
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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T-Lymphocytes, Helper-Inducer / microbiology
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Th1 Cells / microbiology
Substances
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Growth Inhibitors
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Interferon Type I
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Interleukin-12 Subunit p40
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Interleukin-17
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Receptor, Interferon alpha-beta
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Interferon-gamma